P.2.a.044 Efficacy of trazodone in primary insomnia; a double-blind randomised placebo controlled polysomnographic study

P.2.a Affictive disorders and antidepressants - Affective disorders (clinical)

Despite we found no significant difference between the antidepressants in terms of time to discontinuation in a relatively small sample, these results need to be replicated in larger samples. Table. Adjusted medication continuation/discontinuation rates for the six antidepressant studied

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Median time to discontinuation (days) 74 129 143 30-day continuation rate (%) 63.2 72.2 79.1 180-day continuation rate (%) 15.8 27.8 34.9 365-day continuation rate (%) 5.3 5.6 14

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References [1] Laukkala T, Isometsa E, Hamalainen J, Heikkinen M, Lindeman S, Aro. 2001 Antidepressant treatment of depression in he Finnish general population. Am J Psychiatr 158:2077-2079

IP.2.a.0431 Psychoticism dimension in a population of patients with non-psychotic major depression disorder V. Mantua1 ., S. Calugi 1 , E. Schiavi 1 , M. Miniati 1 , G.B. Cassano 1. 1 University of Pisa, Psychiatry Neurobiology Pharmacology and Biotechnologies, Pisa, Italy

Sub-clinical psychotic symptoms in the context of Major Depressive Disorder (MDD) may be detectable even before the full blown psychotic phenomenology Previous research has failed to systematically explore psychotic symptoms other than the presence/absence of delusions and hallucinations in MDD. In this study we assessed psychoticism dimension by means of the 6-items "psychotic features factor" of the MOODS-SR self-reported questionnaire [1] in a population of patients with non-psychotic MDD. Items content ranged from interpersonal sensitivity ("I felt very vulnerable") to frank psychotic symptoms ("You heard voices", "You felt surrounded by hostility as if everybody was against you" or "everybody was talking about you"). The Panic-Agoraphobic Spectrum (PAS-SR); the Social Anxiety Spectrum (SHY-SR), the Obsessive-Compulsive Spectrum (OBSSR) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were also administered. Severity of depression was rated using Hamilton Rating Scale for Depression (HDRS-17) The study included 291 subjects diagnosed with non-psychotic MDD by means ofthe SCID-I, personality disorders were assessed using SCID-II interview. Chi-square test or T-test were used, as appropriate, to compare the two groups on clinical variables and ANCOVA, controlling for HDRS-17, was performed to compare the mean scores of the self-report spectrum instruments at two time points: baseline lifetime and beginning of the continuation phase. Mean lifetime scores on psychotic features were 2.8±1.5. Using the cut-off score of 4, derived from ROC analysis, Low Psychoticism (LP) subjects were 182 (63.6%) and High Psychoticism (HP) were 104 (36.3%). lIP subjects have an earlier onset of depressive illness and a lower quality of life. Age of onset was also significantly lower in HP patients with high mania/hypomania (measured

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using the cut-off of 22 of the MOODS-SR manic/hypomanic component) (22.2±9.9 vs 29.l±13.3, p
1P.2.a.0441 Efficacy of trazodone in primary insomnia; a double-blind randomised placebo controlled polysomnographic study L.M. Paterson1 ., D.l Nutt1 , C. Durant1 , S.l Wilson 1 . 1 University of Bristol, Psychopharmacology Unit, Bristol, United Kingdom Trazodone is a licensed antidepressant and is effective in treating insomnia associated with depressive illness [1]. In addition, it is currently the 2nd most prescribed drug for primary insomnia in the US, despite a lack of objective evidence to support this 'off-label' use [2]. The sleep promoting effects of trazodone may involve 5-HT2A antagonism, a mechanism which is thought to promote slow wave sleep (SWS) and improve sleep continuity [3]. Its pharmacology also includes antihistaminergic (HI) and adrenergic (<1-1 and <1-2 adrenoceptor) effects, which could also lead to sedation. Current drugs licensed specifically for insomnia primarily address sleep onset, and there is still an unmet clinical need to develop sleep promoting agents that treat middle insomnia, tackle poor sleep quality and do not produce dependence. This trial therefore sought to determine the efficacy of trazodone in primary (psychophysiological) insomnia. We assessed the effects of a single dose of trazodone (100 mg) on polysomnographic and subjective sleep measures in patients with a diagnosis of psychophysiological insomnia. Home polysomnography was performed in 12 patients who met the criteria for primary insomnia, had no concomitant psychotropic medication that might affect sleep measures and no hypnotic use for 7 days prior to the study. Subjects received matched placebo

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P.2.a Affictive disorders and antidepressants - Affective disorders (clinical)

or trazodone capsules, 2 h prior to usual bedtime in a doubleblind, randomised crossover design. Study nights were performed at least I week apart. Subjective sleep was assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ) and the St Mary's Hospital Sleep Questionnaire (SMHSQ). Significant differences between groups were determined using the Student's paired t-test. Compared with placebo, trazodone increased total sleep time by 38 minutes (trazodone; 433±19 min, placebo; 395±15 min, P < 0.05), increased SWS due to an increase in stage 3 sleep (trazodone; 129±20 min, placebo; 96±10 min, P < 0.05) and decreased wake after sleep onset (trazodone; 57±20 min, placebo; 77±13 min, P < 0.05). Trazodone also significantly reduced the number of awakenings and reduced spindle density, but did not alter overall sleep efficiency, sleep onset or REM sleep compared with placebo. Significant improvements in subjective sleep were observed; the experience of 'getting to sleep' and 'quality of sleep' were improved in the LSEQ, without adversely affecting 'awakening from sleep' or 'behaviour following wake' factors, indicating lack of a significant morning hangover effect. Similarly, increases in 'sleep satisfaction' and 'sleep quality' score were obtained in the SMHSQ. To our knowledge, these data are the first to report objective polysonmographic effects of trazodone on sleep in primary insomnia in a double-blind, randomised controlled trial. Data suggest that acute trazodone administration at night is an effective sleep promoting agent in psychophysiological insomnia, and may be useful for treating middle insomnia and sleep continuity. References

[I] Kaynak H, Kaynak D, Gozukinnizi E, Guillemioault C. (2004) The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med 5(1), 15-20 [2] Mendelson WB (2005) A review of the evidence for the efficacy and safety of trazodone io iosomuia. J Clin Psychiatry 66(4), 469-76 [3] Teegarden BR, Al Shamma H, Xiong Y. (2008) 5-HT(2A) inverseagonists for the treatment of insomnia. Curr Top Med Chern 8(11), 969-76.

Ip.2.a.0451 Depressed patients show altered neural responses to an emotional Stroop task after response to citalopram treatment E. Pegg1 ., D. Arnone1, S. McKie 1, R. Elliott1, lEW Deakin1, I.M. Anderson1 . 1 University of Manchester, Neuroscience and Psychiatry Unit G907 Stopford Building, Manchester, United Kingdom Introduction: Negative biases in emotional processing have been repeatedly demonstrated in depression and may help maintain the depressed state. The emotional Stroop task has been used to measure increased attention to emotionally valenced words in depression and abnormal neural responses to negative Stroop words have been demonstrated in unmedicated, acutely depressed patients [1]. Previous research has shown antidepressant administration in healthy participants to be associated with enhanced processing of positive and attenuated processing of negative information, both behaviourally and neuronally [2]. Antidepressant treatment and remission from depression have also been associated with normalisation of such biases and abnormalities in patients. Using functional magnetic resonance imaging (fMRI) with depressed patients, decreased neural responses to sad stimuli and increased neural responses to happy stimuli have been demonstrated after sustained antidepressant treatment, mainly using face emotion

processing tasks (e.g. 3). However, no study has used an emotional Stroop task to examine antidepressant treatment response. Methods: 13 unmedicated, currently depressed participants were scanned twice, at baseline and after 8 weeks of citalopram (20-40 mg) treatment. Participants completed an emotional Stroop task during MR scanning. This task was a blocked design, with 10 baseline, 5 neutral, 5 positive and 5 negative blocks. Each block contained 10 words, presented in red, yellow, green or blue text. Words were presented for 2300ms, with a 500ms inter-stimulus interval. Participants identified the colour of the text with a button press. Scanning was conducted on a 1.5T Philips Intera MRl scanner using a whole brain coverage protocol (TR/TE=2000/37ms, 29 axial slices, voxel size=3.5x3.5x5 rom). Results: At 8 weeks, all participants had responded to treatment (measured by a reduction in Montgomery Asperg Depression Rating Scale, MADRS, score of at least 50%). Neuroimaging data were analysed using SPM5. Participants showed extensive increased neural responses to positive words (relative to neutral) at 8 weeks compared to the baseline session in a wide range of regions including amygdala, hippocampus, cingulate gyrus, putamen, thalamus, medial prefrontal cortex and parietal and temporal regions (all p < 0.05 whole brain FDR corrected). In response to negative words (relative to neutral), participants had decreased neural responses at 8 weeks in bilateral middle temporal gyrus and lateral prefrontal cortex (p < 0.001 uncorrected). Discussion: Eight weeks of successful citalopram treatment was associated with increased neural responses to positively valenced and decreased neural responses to negatively valenced Stroop stimuli, in regions previously implicated in depression and emotional processing. This is consistent with previous longitudinal neuroimaging studies of antidepressant treatment response, and findings that citalopram reduces negative and increases positive emotional processing biases. This alteration of emotional processing may be a mechanism of citalopram's antidepressant action. Acknowledgement: This research was supported by the Medical Research Council UK and conducted at the Wellcome Trust Clinical Research Facility, Manchester. References

[I] Mitterschiffihaler, M. T., Williams, S. C. R., Walsh, N. D., Cleare, A. J., Donaldson, C., Scott, J. et al. 2008. Neural basis of the emotional Stroop interference effect io major depression. Psychological Medicioe, 38, 247-256. [2] Harmer, C. J. 2008. Serotonio and emotional processiog: Does it help explain antidepressant drug action? Neuropharmacology, 55, 10231028. [3] Fu, C. H. Y., Williams, S. C. R., Brammer, M. J., Suckliog, J., Kim, J., Cleare, A. J. et al. 2007. Neural responses to happy facial expressions io major depression following antidepressant treatment. American Journal of Psychiatry, 164, 599--607.